This proposal is aimed at understanding the role of centrifugal neuromodulatory feedback loops in early sensory processing. The nervous system regulates information processing even in early sensory areas so as to meet the evolving behavioral demands placed on an organism. A substantial body of evidence suggests that flexibility in early sensory information processing is enabled by centrifugal inputs from basal forebrain and brainstem neuromodulatory structures known to be involved in higher- level functions such as attention, arousal, and reward. Among early sensory processing areas, the olfactory bulb (OB) receives an extensive array of centrifugal inputs which are directly integrated with primary sensory input from olfactory receptor neurons. Accumulating evidence suggests that olfactory perception, particularly under demanding conditions, can be altered by manipulating cholinergic as well as noradrenergic signaling within the olfactory bulb (OB). The present proposal uses combined electrophysiological and behavioral methods to addresses the role of early sensory processing in the regulation of cholinergic and noradrenergic inputs to the OB. Neural activity in the horizontal limb of the diagonal band of Broca (HDB) and locus coeruleus (LC) will be recorded in rats performing a forced-choice olfactory discrimination task in which we systematically alter sensory demands by making the task more difficult. We expect to find enhanced activation in both the HDB and LC when sensory processing demands increase. To examine, in turn, how the activation of these areas alters sensory processing in order to satisfy behavioral demands, we will investigate how stimulation of the cholinergic and noradrenergic inputs to the OB alters the rate and temporal response properties of mitral/tufted cells, the principle output neurons of the OB. We expect to find that activation of cholinergic and noradrenergic inputs serve complimentary roles in sharpening spatial-temporal odor representations in the OB and that these effects will lead to enhanced discrimination of perceptually similar odors. Together, the studies proposed here will improve our understanding of the role that centrifugal feedback loops play in early olfactory information processing. PUBLIC HEALTH RELEVANCE: Neuromodulatory inputs to early sensory areas modulate sensory perception and learning. Disruption of these pathways leads to impairments in sensory information processing. Given that dysfunction in these pathways is linked with numerous diseases and disorders (e.g., Alzheimer's, schizophrenia), understanding how neuromodulatory inputs to early sensory areas regulate sensory information processing is of huge potential benefit. Sasha Devore NRSA 11-08-10